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• W1016465732 abstract "Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide and affects approximately 300 million new individuals each year. HPV is considered the primary etiological agent involved in the development of cervical cancer and causes half a million cases per year worldwide. Prevention of genital HPV infection through immunization has led investigators to employ a number of strategies to develop candidate HPV vaccines. Until today, two different vaccines are available on the market: a quadrivalent vaccine that protects against HPV types 16, 18, 6, and 11 (Gardasil®, Merck Sharp and Dohme), and a bivalent vaccine that protects against HPV types 16 and 18 (Cervarix™, Glaxo SmithKline). Current data regarding the efficacy of these vaccines derive mainly from studies performed by the manufacturers and standardized assays are not commercially available to measure HPV immunity. In this context, the aim of this PhD research project is to set up and standardize HPV pseudovirion-based neutralization (PBNA) and enzyme-linked immunosorbent (ELISA) assays and to use these tests to evaluate and compare the immunogenicity and cross-reactivity levels of the two prophylactic HPV vaccines, which are offered free in Italy to 12-year old girls and are recommended to women aged 12-45 years, according to World Health Organization (WHO) guidelines. First, pseudovirions of HPV types 6, 11, 16, 18, 31, 45, 52, 58 were obtained with a titer of 109 transducing units/ml and neutralization and ELISA assays standardized. Subsequently, a cross sectional study to evaluate the humoral immune response against HPV-volunteers, adolescents, and healthy vaccinated adults with Gardasil® or Cervarix™ was approved by ethics committee of University Hospital of Padua. Comprehensive results were obtained from a group of 100 subjects from Veneto Region, where the quadrivalent Gardasil® vaccine was offered. The study group included 81 subjects investigated within 1-6 months after the completion of the three doses of vaccine and 7, 7, and 5 subjects investigated at 2, 3, and 4 years after vaccination, respectively. At 1-6 months after the completion of the vaccination cycle, 100% vaccinees had neutralizing antibodies (NAbs) against HPV16, 98,8% had NAbs against HPV18, while 91% had NAbs against HPV6 and 50% had NAbs against HPV11. The NAbs titer ranged widely from 1:40 to over 1:10,240 and was lower for NAbs against HPV6 and HPV11 as compared with NAbs titers against HPV16 and HPV18. A progressive reduction of NAbs titer was observed over time and, at 4 years from vaccination, 80% of subjects had NAbs against HPV16, HPV18 and HPV6, and 60% against HPV11. Low level cross-NAbs titer against HPV31 (1:40) was detected in 50% (3/6) of subjects at 1-6 months after vaccination, while no cross-NAbs were detected against HPV45, HPV52 and HPV58. We also evaluated the presence of HPV type-specific NAbs in a group of 6 young girls vaccinated with CervarixTM at 1-6 months after the completion of the vaccination cycle. All subjects presented specific NAbs against HPV16 and HPV18. Titers were higher as compared with titers observed in Gardasil® vaccinated subjects. 100% of subjects presented also cross-NAbs against HPV31, whereas 16,6% presented cross-NAbs against HPV45 and HPV58. None presented cross-NAbs against HPV52.Thanks to these results we can conclude that high-level NAbs were induced with both Gardasil® and CervarixTM vaccines. For the first vaccine, we observed the decline of NAbs titers and the limited cross-neutralization against HPV31. For the second one, cross-neutralizing NAbs were observed against HPV31 in all subjects, together with the presence of NAbs against HPV45 and HPV58 in some subjects." @default.
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• W1016465732 date "2013-01-27" @default.
• W1016465732 modified "2023-09-26" @default.
• W1016465732 title "Evaluation of HPV type-specific antibody response induced by the prophylactic quadrivalent vaccine" @default.
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